Injury to the brain, such as occurs following stroke, often results in a functional behavioral deficit or disability. The magnitude of the deficit or disability is determined both by tissue loss to the infarct as well as the amount of reorganization or "plasticity" that can take place in the reorganized brain tissue. The overall goal of the proposed research in this PPG is to develop a body of knowledge that will identify neural mechanisms amenable to rehabilitative intervention reduce or that would ameliorate motor deficits or disabilities following injury. The program project has four scientific projects and one core. The projects bring complimentary tools to bear on understanding the neuronal events involved in the rehabilitative process in human to non-human primate brain. A strength of this approach is that it allows application of a combination of techniques in a coordinated fashion to investigate cortical reorganization and functional rehabilitation. Transcranial magnetic stimulation (TMS) studies are proposed in Project 1 to allow us to functionally map reorganized regions of the brain and assesses the functional significance of any cortical reorganization with respect to limb movement. Project 2 allows the acquisition of fine spatially resolved maps of physiological cortical consequence as measured in Project 1 by TMS. Project 3 will allow us to understand the reorganizational process at the single unit level of analysis. This utilizes the many neuron recording procedures in macaque monkeys, due to their close relation to humans and because of similarity in motor performance. The types of infarcts to be induced are identical to those seen in the human population in projects 1 & 2, and use many of the same behavioral measures. Single unit recording data can then be compared with the fMRI and TMS data obtained in projects 1 & 2. In project 4 we will utilize the same recording techniques and behavioral measures as in project 3 but will assess the effects of brain damage by making direct focal ablations of the same cortical regions involved in stroke as determined in Project 3. Thus, project 4 will help us to identify the specific regions of the brain responsible for the functional deficits following strokes in Project 3. In addition, project 4 will determine which regions are most crucial in the beneficial reorganizational process following recovery from such lesions.